Guidewire with chemical sensing capabilities

ABSTRACT

A guidewire with a sensor which can detect NO and/or superoxide levels is disclosed. This invention can be useful for in vivo analysis of vascular health.

CROSS REFERENCE

This application is a continuation of application Ser. No. 09/967,186,filed on Sep. 28, 2001, now U.S. Pat. No. 7,025,734, which isincorporated herein by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to physiological sensors and methods of using thesame. More particularly, this invention relates to a guidewire with achemical sensor and a method of using the guidewire.

2. Description of the Background

Atherosclerosis refers to a thickened area in the wall of an arterywhich can partially or completely obstruct the vessel. Most instances ofmyocardial infarction, cardiac arrest, or stroke are caused by rupture,fissure, or ulceration of the atherosclerotic lesion. The rupture,fissure, or ulceration causes a large thrombus to form in the artery,which can completely occlude the flow of blood through the artery,thereby injuring the heart or brain.

Treatment modalities for atherosclerotic coronary artery disease caninclude percutaneous transluminal interventions (PTI) such as balloonangioplasty. PTI can relieve myocardial ischemia in patients withcoronary artery disease by reducing lumen obstruction and improvingcoronary flow. Recurrent stenosis or restenosis, characterized by thereocclusion of the coronary artery following PTI remains a significantproblem, however. Development of restenosis, typically within 6 monthsafter the procedure, results in significant morbidity and mortality orfrequently necessitates further interventions such as repeat angioplastyor coronary bypass surgery.

Reactive oxygen species in general, and the molecule nitric oxide (NO)in particular, are key entities in the processes of atherosclerosis andrestenosis. In endothelial cells, NO is formed from the metabolism ofL-arginine by endothelial NO synthase (Oeamar et al., “ReducedEndothelial Nitric Oxide Synthase Expression and Prosuction in HumanAtherosclerosis” Circulation 1998, v. 97, 2494-2498). Under normalhemodynamic conditions, the production of NO inhibits such processes asmonocyte adherence and chemotaxosis, platelet adherence and aggregation,and vascular smooth muscle proliferation, all of which are potentialcauses of atherosclerosis and restenosis. In contrast, reduced NOexpression has been associated with increased endothelial adhesivenessfor monocytes and increased lesion formation in pathological rabbitmodels (Niebauer et al., “Local L-Arginine Delivery After BalloonAngioplasty Reduces Monocyte Binding and Induces Apoptosis.” Circulation1999, v. 100, 1830-1835). Accordingly, NO is as a key entity in thebalance of metabolic and biological processes involved in atherogenesisand restenosis.

Because of the small concentrations of NO expected in vivo, a morecomplete understanding of sample biological environments can be obtainedby making measurements of superoxide concentration in addition to orindependent of NO measurements. Superoxide is a key molecular entity indetermining the balance of NO released by the endothelium. Superoxidefree radicals can be released by activated monocytes and can counteractNO, in effect neutralizing the beneficial properties of NO (Hishikawaand Luscher, “Pulsatile Stretch Simulates Superoxide Production in HumanAortic Endothelial Cells” Circulation 1997, v. 96, 3610-3616). The ratioof NO concentration to superoxide concentration can therefore be a moreuseful measure than either concentration alone.

Percutaneous treatment strategies for conditions such as atherosclerosisand restenosis are almost always performed without the benefit ofspecific knowledge of the biological environment of the lesion. Whilethe procedures are usually initially successful, six month restenosisrates of 30% or higher are not uncommon post-procedure outcomes.Therefore, the ability to monitor the level of NO and/or superoxidepresent in the immediate vicinity of a lesion could provide importantinformation necessary for a physician to obtain a clearer understandingof the relative condition of the lesion. For example, low NO and highsuperoxide concentrations could indicate impaired endothelium. As aresult, procedures could be optimized based on individual lesion status.

Detection methods for both NO and superoxide in biological vessels andtissue are presently available. Chemoluminescent NO sensors can employ aNO sensing compound, typically containing iron, manganese, cobalt,platinum, osmium, and/or ruthenium, imbedded in a film or plug which isincorporated into the end of a fiber optic sensor. The opticalcharacteristics of the NO sensing compound when exposed to the vessel ortissue is determinative of the NO concentration.

Other NO sensors employ methods including mass spectrometry, use ofhigh-pressure cadmium columns (by measuring NO by-products), dithioniteand hemoglobin treatment, solution methods, and electrical resistanceacross an electrode having a catalytic material capable of catalyzingoxidation of NO coated with a cationic exchanger. Superoxide detectionmethods are similar.

Accordingly, it would benefit medical professionals to be able toanalyze NO and superoxide levels in vivo, and, if treatment is decidedupon at the time of analysis, also begin entry of a treatment catheterwith minimal additional time, energy, and medical devices.

SUMMARY OF THE INVENTION

In accordance with one aspect of the embodiments of the invention, aguidewire for biological luminal placement is provided. The guidewireincludes an elongated wire assembly and a sensor for measuring the levelof nitric oxide or superoxide molecules in a particular area of thepatient's body. The elongated wire assembly can be configured to allow acatheter assembly to be slidably disposed over at least a portionthereof.

In one embodiment, the sensor comprises a compound that can react withnitric oxide or superoxide such that subsequent to the reaction of thecompound with nitric oxide or superoxide, the optical properties of thecompound change. An optical system can be provided for measuring theoptical properties of the compound. The optical system can include afirst fiber optic line for illuminating a light on the compound and asecond fiber optic line to receive the light from the compound and torelay the received light to a detector.

In accordance with another embodiment, the sensor comprises anelectrically conductive substrate having an amperometric response thatis substantially unaffected by the presence of nitric oxide orsuperoxide and a coating for reacting with nitric oxide or superoxide soas to cause a change in the electrochemical potential of the nitricoxide or superoxide.

In one embodiment, the sensor can comprise a catalytic material capableof oxidizing nitric oxide or superoxide.

In accordance with another aspect of the embodiments of the invention, adiagnostic method is provided comprising positioning an elongated wireassembly into a vessel, the wire assembly including a sensor formeasuring the level of nitric oxide or superoxide; guiding the wireassembly to a designated region within the vessel; and measuring thelevel of nitric oxide or superoxide in the region of the vessel. Themethod can further comprise inserting a catheter over the wire assemblyto treat the region of the vessel. In one embodiment, a stimulant can bedelivered to increase the production of nitric oxide or superoxide. Theelongated wire can be used for the treatment of thrombosis orrestenosis.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side view showing a partial cross section of an embodimentof the inventive guidewire with a chemical sensor.

FIGS. 2-3 are side views of various embodiments of the most distal partof the core section of the guidewire.

FIG. 4 is a close-up of section 4 of FIG. 1 showing the connectingelement of an embodiment of the guidewire in FIG. 1.

FIG. 5 illustrates another embodiment of the connecting element of theguidewire.

FIGS. 6-9 illustrate various embodiments of the distal end section ofthe distal core.

FIGS. 10-11 illustrate various fiber optic embodiments of the chemicalsensor.

FIG. 12 shows a monomeric porphyrin structure that can be used in anembodiment of the chemical sensor.

FIG. 13 shows another monomeric porphyrin structure that can be used inan embodiment of the chemical sensor.

FIG. 14 shows a tetramethylpypridylporphyrin (TMPP) structure that canbe used in an embodiment of the chemical sensor.

FIG. 15 shows a protoporphyrin IX dimethyl ester (DME) structure thatcan be used in an embodiment of the chemical sensor.

DETAILED DESCRIPTION

An apparatus and method to perform therapeutic treatment and diagnosisof a patient's vasculature through the use of a guidewire having atleast one chemical sensor incorporated therein are described. Theinventive apparatus and method is particularly described with regard toNO and superoxide sensors used with a guidewire. The present inventionis designed with the intent of use in vivo. Although the guidewire ofthe present invention can aid in loading a catheter for balloonangioplasty, drug delivery, or any other suitable treatment purposes,the guidewire can also act as a standalone diagnostic or treatmentdevice.

Guidewire

FIG. 1 shows one embodiment of a guidewire 10 adapted to perform atherapeutic or diagnostic treatment. The use of the guidewire 10 is notlimited to the treatment and diagnosis of a patient's vascular system,but can also include use with the esophagus, stomach, colon, uterus,joints, brain, liver, kidneys, ureter, urethra, bladder, mouth,nostrils, lungs, muscles, saphenous vein grafts or internal mammaryartery grafts (and other arterial grafts such as radial grafts), and anyother bodily organ capable of receiving a guidewire. Depending on thetype of application in which it is to be used, the guidewire 10 can beused in conjunction with a variety of intravascular or intraluminaldiagnostic or treatment devices, including balloon dilatation catheters(e.g., for percutaneous transluminal coronary angioplasty (PTCA)procedures), intravascular or intraluminal stents, directionalatherectomy devices, drug delivery devices, radiation treatment devices,and devices for placing or retrieving vaso-occlusive coils.

During use of the particular embodiment in FIG. 1, a chemical sensor 12attached to the guidewire 10 can be exposed, at the distal tip 14, tothe fluid (e.g., blood) of the patient. This exposure can occur throughan opening 16 of the guidewire 10. The guidewire 10 can also beoperatively coupled to a variety of other diagnostic or treatmentdevices for organs or tissues, including intramuscular electrodedevices, cerebral/cranial electro-stimulation devices, biopsy devices,drug delivery devices, radiation treatment devices, fluid drainagedevices, organ implant devices, or any other diagnostic or treatmentdevice for organs or tissues.

The guidewire 10 includes an elongated core member that includes arelatively high strength, hypotube-shaped proximal core section 18 and arelatively flexible distal core section 20. Depending on manufacturingpreferences, the guidewire 10 can include a connecting element 22 thatjoins a distal end 24 of the proximal core section 18 and a proximal end26 of the distal core section 20 of the guidewire 10.

The proximal core section 18 of the guidewire 10 can be generally about130 cm (51 in.) to about 270 cm (106 in.) in length with an outerdiameter of about 0.15 mm (0.006 in.) to about 0.45 mm (0.018 in.) forcoronary use. Larger diameter guidewires (e.g., up to 0.89 mm (0.035in.) or more) can be employed in peripheral arteries and other bodylumens.

In the embodiment shown in FIG. 1, the distal core section 20 has atleast one tapered section 28 that becomes smaller in radius with respectto the distal direction. The tapered shape of the distal core section 20enhances the mechanical performance of the guidewire 10 by providing astiffness gradient over the length of the distal core section 20.Alternatively, the distal core section 20 can have a non-tapered shape,which generally simplifies the manufacturing process.

In one embodiment, the proximal core section 18 and the distal coresection 20 are each formed from a hypotube made of stainless steel or ofa pseudoelastic alloy material, such as a nickel-titanium (NiTi) alloy(e.g., nitinol). The NiTi alloy material can include about 30% to about52% titanium and the balance nickel and up to about 10% of one or moreother alloying elements. The other alloying elements can include iron,cobalt, vanadium, platinum, palladium and copper. The alloy can, forexample, contain up to about 10% copper and vanadium and up to about 3%of the other alloying elements. The proximal core section 18 can besignificantly stronger than the distal core section 20. Suitable highstrength materials include 304-stainless steel, which is a conventionalmaterial in guidewire construction. Other high strength materialsinclude nickel-cobalt-molybdenumchromium alloys such as commerciallyavailable MP35N alloy.

The connecting element 22 can be configured as a sleeve or hollow memberthat slightly overlaps the distal end 24 of the proximal core section 18and the proximal end 26 of the distal core section 20. Various shapesand configurations of the distal core section 20 can be practiced withinthe scope of this invention.

A flexible coil 30, generally having a helical configuration, can bedisplaced around the distal core section 20. The flexible coil 30 can besecured at its distal end to the distal end of a shaping ribbon 32 by amass of bonding material, such as solder, which forms a rounded tip 34when it solidifies. The proximal end of the flexible coil 30 can besecured to the distal core section 20 at a proximal location 36 and atan intermediate location 38 by a suitable bonding material. The proximalend of the shaping ribbon 32 can be secured to the distal core section20 at the same intermediate location 38 by bonding material. The mostdistal section of the flexible coil 30 can be made of radiopaque metal,such as platinum or platinum-nickel alloys, to facilitate thefluoroscopic observation of the guidewire 10.

The flexible coil 30 can be about 3.0 cm (1.2 in.) to about 45 cm (18in.) in length, more narrowly about 5.0 cm (2.0 in.) to about 20 cm (7.9in.), can have an outer diameter about the same size as the outerdiameter of the elongated proximal core section 18, and can be made froma wire of about 0.025 mm (0.001 in.) to about 0.08 mm (0.003 in.) indiameter, for example about 0.05 mm (0.002 in.) in diameter. The shapingribbon 32 can have a generally rectangular-shaped transversecross-section, with a width, for example, of about 0.025 mm (0.001 in.),and a height, for example, of about 0.076 mm (0.003 in.).

As shown in FIGS. 2 and 3, a distal end 40 of the distal core section 20can be tapered and plunge-grounded to a specific length, or flattenedinto a rectangular cross-section (not shown). Plunge-grinding, as knownby one having ordinary skill in the art, is a centered form of grindingin which the grinding tool's wheel “plunges” radially into the part. Inthe embodiment shown in FIG. 2, the most distal end 40 of the distalcore section 20 can have a taper length 42 and a distal plunge-groundlength 44. The taper length 42 can be in the range of about 4.0 cm (1.6in.) to about 7.0 cm (2.8 in.), for example about 5.0 cm (2.0 in.). Thedistal plunge-ground length 44 can be typically in the range of about6.0 cm (2.4 in.) to 10.0 cm (3.9 in.), for example about 5.0 cm (2.0in.). The lengths 42 and 44 depend in part upon the stiffness orflexibility desired in the final product.

The outer diameter of the plunge-ground portion of the most distal end40 can be in the range of about 0.015 cm (0.006 in.) to about 0.046 cm(0.018 in.), with one embodiment having an outer diameter of about0.0267 cm (0.0105 in.). For the alternative embodiment having the mostdistal end 40 of the distal core section 20 just plunge-ground to aspecific length (as shown in FIG. 3), distal plunge-ground length 44 canbe the range of about 1.7 cm (0.67 in.) to about 2.2 cm (0.87 in.), forexample about 2.0 cm (0.79 in.). If desired, the most distal end 40 canalso be provided with a rounded tip made out of solder or other suitablematerial to prevent its passage through the spacing between thestretched distal section of the flexible coil 30 (shown in FIG. 1).

FIG. 4 shows a cross-sectional side view of the connecting element 22 ofthe guidewire 10. The connecting element 22 can be a hollow elongatedelement that receives the proximal end 26 of the distal core section 20and the distal end 24 of the proximal core section 18. By facilitatingthe connecting element 22, the proximal core section 18 of the guidewire10 can be in a torque transmitting relationship with the distal coresection 20 of the guidewire 10. The sensor 12 can be positioned extendedwithin a lumen 46 and disposed through the proximal core section 18, theconnecting element 22, and the distal core section 20.

The connecting element 22 joining the proximal core section 18 with thedistal core section 20 can be a NiTi or stainless steel sleeve. Theconnecting element 22 can be bonded to the distal end 24 of the proximalcore section 18 and the proximal end 26 of the distal core section 20.Bonding of the connecting element 22 can be done using any method knownto those having ordinary skill in the art, including laser bonding,thermal bonding, or with an adhesive 48, including adhesives cured withultraviolet (UV) light, such as Loctite.

In the embodiment shown in FIG. 5, the connecting element 22 joining theproximal core section 18 with the distal core section 20 is a polyimidejacket (or tubing). The jacket can be bonded to the distal end 24 of theproximal core section 18 and the proximal end 26 of the distal coresection 20 with the adhesive 48.

The connecting element 22 generally has an outer diameter in the rangeof about 0.025 cm (0.010 in.) to about 0.089 cm (0.035 in.), with aninner diameter in the range of about 0.020 cm (0.008 in.) to about 0.084cm (0.033 in.). The overall length of the connecting element 22 can bein the range of about 0.25 cm (0.098 in.) to about 3.0 cm (1.2 in.),more narrowly in the range of about 0.75 cm (0.30 in.) to about 1.5 cm(0.59 in.).

In FIGS. 6-9, various alternate embodiments of the distal end 40 of theguidewire 10 are illustrated. FIG. 6 illustrates an embodiment with theshaping ribbon 32 inserted under the flexible coil 30, overlapping thedistal end 40 of the distal core section 20. The shaping ribbon 32 canthen be soldered in place. Further, a chemical sensor tip 50 can bedisposed within the lumen 46 and distally ends in the rounded tip 34.

The rounded tip 34 of the guidewire 10 can be a clear polymericatraumatic tip formed by coupling a clear polymeric material sheath ortube to the flexible coil 30. Alternatively, the rounded tip 34 can alsobe a metal atraumatic tip. The metal tip can be formed by the solderingmaterial used to couple the distal end of the flexible coil 30 to theshaping ribbon 32. With either the metal or polymeric tip configuration,the chemical sensor tip 50 disposed within the lumen 46 can be bent awayfrom the centerline of the distal end 40 to potentially improve chemicalreception (illustrated in FIG. 7).

In FIGS. 8 and 9, the sensor 12 extends longitudinally through the lumen46 of a polymeric jacket 52. In FIG. 9, the distal core section 20 canbe in the form of a reinforcing mandrel.

Catheter

In the embodiments shown herein, the guidewire 10 can be constructed tobe able to receive a catheter. The catheter typically slideslongitudinally along and over the guidewire 10. The inside diameter ofthe catheter can be larger than the outside diameter of the guidewire 10to provide for sliding.

Any treatment or diagnosis catheter or device with an appropriatelysized and shaped lumen can be used with the guidewire including drugdelivery catheters, scopes (endoscopes, arthroscopes, laproscopes,cardioscopes, etc.), dilatation catheters (e.g. balloon catheters),vaso-occlusive coil delivery and/or retrieval devices, stent deliverydevices (including balloon dilatation catheters), implant deliveryand/or retrieval devices, etc.

Drug delivery catheters or stents can be used to administer any numberof active agents. The active agent can be for inhibiting the activity ofvascular smooth muscle cells. More specifically, the active agent can beaimed at inhibiting abnormal or inappropriate migration and/orproliferation of smooth muscle cells for the inhibition of restenosis.The active agent can also include any substance capable of exerting atherapeutic or prophylactic effect in the practice of the presentinvention. For example, the agent can be for enhancing wound healing ina vascular site or improving the structural and elastic properties ofthe vascular site. Examples of agents include antiproliferativesubstances such as actinomycin D, or derivatives and analogs thereof(manufactured by Sigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee,Wis. 53233; or COSMEGEN available from Merck). Synonyms of actinomycin Dinclude dactinomycin, actinomycin IV, actinomycin I₁, actihomycin X₁,and actinomycin C₁. The active agent can also fall under the genus ofantineoplastic, anti-inflammatory, antiplatelet, anticoagulant,antifibrin, antithrombin, antimitotic, antibiotic, antiallergic andantioxidant substances. Examples of such antineoplastics and/orantimitotics include paclitaxel (e.g. TAXOL® by Bristol-Myers SquibbCo., Stamford, Conn.), docetaxel (e.g., Taxotere®, from Aventis S. A.,Frankfurt, Germany) methotrexate, azathioprine, vincristine,vinblastine, fluorouracil, doxorubicin hydrochloride (e.g., Adriamycin®from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g., Mutamycin®from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of suchantiplatelets, anticoagulants, antifibrins, and antithrombins includesodium heparin, low molecular weight heparins, heparinoids, hirudin,argatroban, forskolin, vapiprost, prostacyclin and prostacyclinanalogues, dextran, D-phe-pro-arg-chloromethylketone (syntheticantithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membranereceptor antagonist antibody, recombinant hirudin, and thrombininhibitors such as Angiomax a (Biogen, Inc., Cambridge, Mass.). Examplesof such cytostatic or antiproliferative agents include angiopeptin,angiotensin converting enzyme inhibitors such as captopril (e.g.,Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.),cilazapril or lisinopril (e.g., Prinivil® and Prinzide® from Merck &Co., Inc., Whitehouse Station, N.J.), calcium channel blockers (such asnifedipine), colchicine, fibroblast growth factor (FGF) antagonists,fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (aninhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand nameMevacor® from Merck & Co., Inc., Whitehouse Station, N.J.), monoclonalantibodies (such as those specific for Platelet-Derived Growth Factor(PDGF) receptors), nitroprusside, phosphodiesterase inhibitors,prostaglandin inhibitors, suramin, serotonin blockers, steroids,thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), andnitric oxide. An example of an antiallergic agent is permirolastpotassium. Other therapeutic substances or agents which can beappropriate include alpha-interferon, genetically engineered epithelialcells, rapamycin and dexamethasone.

Chemical Sensors

Referring again to the embodiment in FIG. 1, the sensor 12 can befixedly coupled to the guidewire 10 at least at one coupling location51. Alternatively, the sensor 12 can be operatively coupled to theguidewire 10. In this configuration, the sensor 12 can be longitudinallyslideable, transversely shiftable, and rotationally movable within theguidewire 10.

In one embodiment, the sensor 12 can have an outer diameter in the rangeof about 10 μm to about 1000 μm. Other sensor diameters are also withinthe scope of this invention, including those of approximate outerdiameters of 30 μm, 200 μm and 250 μm. Regardless of diameter, sensorscan provide the guidewire 10 with the ability to sense vessel and bloodcharacteristics, including but not limited to concentration, density,gross volume, mass, molarity, and/or particle count of NO and/orsuperoxide and other oxygen containing molecules.

The sensor 12 can extend longitudinally through the lumen 46 of thedistal core section 20 of the guidewire 10 as well as through theconnecting element 22 and the proximal core section 18. For theembodiment shown in FIGS. 8 and 9, the sensor 12 extends longitudinallythrough the polymeric jacket 52, immediately below the distal coresection 20, as well as through the connecting element 22 and theproximal core section 20. In the embodiment shown in FIG. 9, the distalcore section 20 can be in the form of a reinforcing mandrel.

As stated above, in one embodiment, the sensor 12 can be exposed to ablood vessel of a patient at the distal tip 14 of the guidewire 10 orthrough the opening 16. The opening 16, such as a window or a cutaway,allows the sensor 12 to be exposed to a patient's vasculature andperform its intended sensing function. The opening 16 can have any sizeand/or shape that is advantageous to sensor 12 and/or the guidewiremanufacturing preferences.

It is understood, however, that the sensor 12 can extend longitudinallyalong either the inside or outside of the proximal core section 18, theconnecting element 22 and the distal core section 20. The sensor 12 canextend beyond both ends of the guidewire 10. The sensor 12 can be incommunication with a data processing system through a mechanicalcoupler. The distal extension of the sensor 12 allows the sensor tip 50to be flush with, or extend slightly out of the distal end 40 of theguidewire 10.

NO Optical Sensors

As shown in FIGS. 10 and 11, the sensor 12 can be an optical NO sensor.The optical NO sensor can have a polymer matrix film or plug 53incorporated into an optical fiber sensor system. NO-sensing compoundsexhibiting sensitivity and selectivity to NO are imbedded in the polymermatrix film or plug 53. The optical properties of the NO-sensingcompounds change upon reaction with NO. NO-sensing compounds that actreversibly or irreversibly with NO can be selected for use in the sensor12.

The NO-sensing compound can be selected from an appropriate porphyrincompound or metal-containing compound such as metalloporphyrins.Possible metals include iron, manganese, cobalt, platinum, osmium, andruthenium. For example, iron-containing compounds suitable for useinclude hemes, of which the compound can include oxyhemoglobin,cytochrome c, hemin, and myoglobin.

A flexible and modular optical system can be required for development ofthe sensor 12. Such an absorption-based system can deliver light into anoptical fiber 54, usually made of silica (glass) or plastic, to excitethe sensor 12, efficiently collect the returned light, and convert it toNO concentration. As needed, signal processing can be incorporated intothe system to eliminate system noise or background. The optical systemcan also be used with fluorescent or phosphorescent sensors underconditions in which luminescent sensors are to be used.

In specific applications, the optical system would include diodes atspecific wavelengths and no grating. In a general description of onesystem, the components of the optical system are optimized for fiberoptic output from a light source 56 and fiber optic input to a detector58. These components, connected by SMA connectors, include:

(1) Fibers 54 and 60. 100 μm silica core, silica clad fibers can be usedin the optical system. Other sizes can also be used including fibers assmall as about 100 nm to about 1000 nm and fibers in the range of about1 μm to about 100 μm.

(2) Light source 56. The sensor design utilizes a continuous tungstenhalogen lamp. This lamp can be replaced with a pulsed source or achopper can be placed in front of the lamp under conditions wherephotodegradation of sensor compounds is determined to occur, or underconditions where synchronization of the source 56 and a detector 58 isdesirable to filter out background noise.

(3) Detector 58. A 1200 lines/mm grating over the range of 400-650 nmdisperses light onto a 1024 element CCD detector with a resolution ofabout 1 nm to about 2 nm. This level of resolution can be adequate formost expected uses of the NO sensor. If improved resolution is required,the grating can be changed, or the diameter of the fiber which goes tothe detector and acts as the entrance slit of the spectrometer can bereduced.

(4) A data system 62. The detector 58 can be connected to a PC through aNational Instruments A/D board. The spectrometer and acquired data canbe driven by Spectrasoft software (World Precision Instruments). Thissoftware, based on LabView software, which is known to those havingordinary skill in the art, can be used to determine the best method ofreading data from the CCD to achieve the desired sensitivity. Forexample, the signal to noise ratio can be altered by use of LabViewsoftware signal processing algorithms if necessary. LabView software canalso be used to perform sensor calibration and display real-time valuesof NO concentrations. Proper sensor design and signal processing in theabove described optical system allows sensitivity of a 0.0001 absorbanceunit change in absorbance equivalent to be achieved.

FIG. 10 shows one embodiment of the sensor 12 design. This dual lumensensor includes the optic fibers 54 and 60. The sensor 12 has an outerdiameter less than 1.0 mm (0.039 in.) as a housing for the two fibers 54and 60. The distal ends of the fibers 54 and 60 can be cut and polishedat about a 45 degree angle, and aluminum or gold evaporated onto thepolished surface to form two mirrors 64 and 65. The fiber 54 transmitslight from the light source 56 to the mirrors 64 and 65. Light travelsfrom the source 56 through fiber 54, is reflected by the mirror 64,travels through the transparent plug 66, then reflects off the mirror65, through the fiber 60, through the plug 53 (which is inserted betweentwo sections of fiber 60), and back through fiber 60 to the detector 58.Light output and input can then be processed by the data system 62.

The length of the section removed from the fiber 60 is a control for thepath length of the absorbing compound, and can be varied as needed tooptimize sensor performance. The NO-sensing compound can be injectedinto a mold containing the sensor 12 and allowed to cure, forming asemi-rigid NO-permeable plug. The fiber with the second mirror (fiber 60in the embodiments shown in the figures) can be aligned before the gelis cured and fixed in place. Prior to assembly, a portion of thesidewall of the sensor 12 can be removed forming the opening 16 thatallows NO gas to permeate to the sensing compound. A notch can beremoved from the center of the sensor forming a gap 68 for light to bereflected between the two fibers. The gap 68 can be filled with thetransparent plug 66.

FIG. 11 shows another variation of this embodiment placing the plug 53at the distal tip of the sensor 12. This removes the need for mirrors 64(shown in FIG. 10). Placing the plug 53 at the distal tip of the sensor12 also provides chemical sensitivity at the most distal point of thesensor 12.

Variations of this embodiment exist. For example, the exposed portion ofthe plug 53 can have a coating imbedded with NO-sensing protein. Thecoating can be relatively inert to NO, such as a particular metal ormetal colloid including gold, silver, tungsten, thoriasol, antimonypentoxide, carbon, red iron oxide, titanium dioxide and platinum.Colloid sizes from 2 nm to 250 nm, and more narrowly of the range from 5nm to 100 nm, provide a foundation for protein attachment. Protein(s)and/or peptide(s) that are dye labeled are then attached to the metalfoundation. The dyes, such as Orange Green fluorophore dyes, can be usedfor protein and/or peptide labeling but should not react to NO.

The protein and/or peptide bind NO. They can also bind NO specifically.Binding specifically is the act of binding with NO, but not binding withinterfering substances. One useful heme-group-containing protein iscytochrome c′. Some sources of cytochrome c′ include, but are notlimited to, microorganisms, more preferably bacterial sources, and moreparticularly, purple phototropic bacteria, aerobic nitrogen-fixingbacteria, and facultatively denitrifying bacteria, and still moreparticularly sources such as C. vinosum, R. purpureus, and R.gelatinosa. The NO-binding compound can also be entrapped in a matrix,such as a silica sol. Furthermore, stabilizers can be used in thecompound.

NO Electrode Sensors

One embodiment of the sensor 12 can be an electrode or multipleelectrodes having a catalytic material capable of catalyzing oxidationof NO coated with a cationic exchanger. These electrodes can be wiresacting as the whole length of the sensor and/or electrodes mounted atthe end of the sensor 12. The sensor 12 provides a direct measurement ofNO through the redox reaction of NO→NO⁺+e⁻ and is selective for NOthrough the discrimination of the cationic exchanger against nitrite(NO₂ ⁻).

Specifically, the NO-specific electrode sensor comprises an electricallyconductive substrate whose amperometric response is substantiallyunaffected by the presence of NO. The electrode also comprises anadherent and substantially uniform electrochemically active polymericcoating which interacts with NO in such a manner so as to cause a changein the redox potential of NO and the electrode sensor.

The electrically conductive substrate can be electrically conductivecarbon (e.g., basal plane carbon, pyrolytic graphite (BPG), or glassycarbon), indium tin oxide, iridium oxide, nickel, platinum, silver, orgold. The preferred electrically conductive substrate will depend inpart on whether oxidation or reduction at the electrode sensor will betaking place during use. For example, a noble metal such as platinum orgold could evolve hydrogen from water reduction which could adverselyaffect the polymer film(s) on the substrate.

This oxidation potential for NO on a standard electrode can be loweredby contact with various materials capable of catalytically oxidizing NO.The current or charge generated by this embodiment can be high enough tobe used as an analytical signal in a microsystem. A working electrode ofthis embodiment can have a conductive solid support with a catalyticsurface for NO oxidation. A catalytic surface on a conductive supportcan be provided using several approaches.

For example, a conductive catalytic material capable of catalyzing NOoxidation can be layered on a conductive solid support. The conductivecatalytic material can be layered on any number of conductive materialscoated on a conductive or nonconductive base material; the conductivecatalytic material can be layered directly on a conductive basematerial; or the conductive catalytic material can itself comprise theconductive support. The electrode can also be fashioned directly fromthe conductive catalytic material or by incorporating or doping acatalyst into the support material. A working electrode of a sensor ofthe described embodiment of this invention preferably can have a solidconductive support coated with one or more layers of a conductivematerial capable of catalyzing oxidation of NO, hereinafter referred toas catalytic material.

Several types of catalytic materials can be used in the sensor, as longas the catalytic material exhibits electronic, ionic or redoxconductivity or semiconductivity, collectively referred to herein asconductivity. The change in the observed current drawn through theelectrode sensor at a particular potential can be correlated to theconcentration of NO in the sample being evaluated. Such materialsinclude, but are not limited to, polymeric porphyrins andpolypthalocyanines. The above-mentioned materials can contain centralmetals, including transition or amphoteric metals. The metallized ordoped polymer can contain any suitable metal which will interact withNO, such as the transition or amphoteric metals and preferably nickel,cobalt, or iron. Polymers which can also be used but require dopinginclude polyvinylmetallocenes (e.g. ferrocene), polyacetylene doped withdifferent metal redox centers and polypyrraline doped with differentredox centers such as, e.g. methyl viologen. Polymeric substitutedglyoximes can also be employed.

Catalytic conductive materials that can be used for a sensor of thepresent invention are metallized polyphthalocyanine or polymericmetalloporphyrins, which are organic p-type semiconductors withrelatively high conductivity and which can be successfully deposited ona supporting conductive material. The metallized polymeric porphyrincompounds should not form metal-oxo bridges (M-O-M) with the substrate.Polymeric metalloporphyins have been shown to have high catalytic effectfor the electrochemical oxidation of several small organic and inorganicmolecules. Bennett, J. E. et al., Chem. Materials 3:490-495 (1991).Polymeric porphyrins polymerized and copolymerized from monomericporphyrinsN,N′-di(5-p-phenylene-10,15,20-tri(3-methoxy-4-hydroxyphenyl)porphyrin,1,10,-phenantroline-4,7-diamine, and 5-p-(pyrole-1-yl)phenylene-10,15,20-tri-(3-methoxy-4-hydroxyphenyl)porphyrin with Fe, Mn,Co and Ni as central metals are useful for this embodiment given theirhigh catalytic effect for selective electrochemical oxidation of NO.Other useful compounds include tetrakis(3-methoxy-4-hydroxyphenyl)porphyrin (TMHPP) and meso-5′-0-p-phenylene-2′,3′-0-isopropylideneuridine-tri(n-methyl-4-pyridinium)porphyrin (PUP), shown in FIGS. 12 and13.

The electrochemically active polymeric coating also can be comprised ofthe metallized polymeric porphyrin compounds of tetramethylpyridinepyrrole and dimethyl ester porphyrin, especially tetramethylpyridinepyrrole (TMPP) and dimethyl ester porphyrin (DME) metallized withnickel, cobalt, and iron. Metallized porphyrin compounds of TMPP and DMEare respectively depicted in FIGS. 14 and 15, wherein M is any suitablemetal ion, such as Ni²⁺, Co²+, or Fe³+, X is a suitable anion to renderthe compound neutral, such as C10₄ ⁻ in the case of TMPP and C1⁻ in thecase of DME, and n is an integer sufficient to render the compoundneutral, such as 4 in the case of Ni²+ and Co²+ TMPP, 5 in the case ofFe³⁺ TMPP, and 1 in the case of Fe³+ DME (not shown).

The electrochemically active polymeric coating should be adherent to andsubstantially uniform over the substrate. While the polymeric coatingcan be of any suitable thickness, a suitable example range is betweenabout 0.01 μm and about 50 μm in thickness. Electrochemically activepolymeric coatings will differ in affinity for various substrates. Theelectrochemically active polymeric coating as used in the presentinventive electrode sensor preferably has a high affinity for theparticular substrate being used.

In order to discriminate against interfering ions and compounds,particularly NO₂ ⁻, the porphyrinic catalysts used in the presentinvention are also preferably covered with a thin layer of a cationicexchanger or gas-permeable membrane to prevent anion diffusion to thecatalytic surface. The gas-permeable membrane coating can be of anysuitable material, preferably a perfluorinated compound such as Nafion®(available from Aldrich Chemical Co., Milwaukee, Wis.), a fluorocarbonpolymer. Suitable cationic exchangers include AQ55D available from Kodakand the stated Nafion®. Nafion® is a negatively charged cationicexchange polymer which prevents diffusion of anions like NO₂ ⁻ to theelectroactive surface of the polymeric porphyrin, but is highlypermeable to NO. The layer of cationic exchanger or gas-permeablemembrane coating deposited onto the surface of the electrode sensor canbe of any suitable thickness, including from about 0.5 μm to about 50μm. The resulting membrane-coated NO electrode sensor is more selectiveto NO than an uncoated electrode due to the membrane exclusion ofinterfering species such as nitrite.

The thin layer of polymeric porphyrin film can be electrochemicallydeposited on any solid conductive support, or a conductive ornonconductive base material coated with any number of conductivematerials, or the conductive catalytic material can itself comprise theconductive support. Conductive support materials particularly suitablefor these sensors include carbon fibers, and gold or platinum wire.

The NO-specific electrodes can be prepared in any suitable manner. Anadherent and substantially uniform coating of an electrochemicallyactive polymer, as previously described, can be formed on a surface ofan electrically conductive substrate, as previously described, by anysuitable means including electrolytic polymerization.

For electrolytic polymerization, the precursor (e.g., monomer, dimer, oroligomer) used to form the electrochemically active polymeric coatingcan be electrolytically polymerized onto a surface of the electricallyconductive substrate. This electrolytic polymerization occurs byimmersing the substrate in an appropriate electrolyte solutioncontaining the precursor in combination with a supporting electrolyte.The electrolyte solution will typically additionally contain a suitablesolvent. Examples of solvents that can be used in the electrolytesolution include acetonitrile, methanol, dimethyl formamide, dimethylsulfoxide, propylene carbonate, and the like. The supporting electrolytecan be a perchlorate, sulfuric acid, phosphoric acid, boric acid,tetrafluoro-potassium phosphate, quaternary ammonium salt, or similarcompound.

The coating of the gas-permeable membrane (e.g., Nafion®) can be appliedonto the sensor by any suitable means. For example, a solution of themembrane material (e.g., Nafion®) can be used to coat the electrode, andthe electrode then can be allowed to dry to produce a uniform film. Thesensitivity of the gas-permeable membrane-coated electrode sensor can befurther increased by soaking the electrode sensor in a sodium hydroxidesolution for at least about 24 hours and preferably a few days.

During use, NO will directly interact with or bind the polymeric coatingon the substrate, thereby changing the redox potential of NO and theelectrode sensor. This interaction changes the current drawn through theelectrode sensor when employed as a working electrode at a particularpotential in a manner related to the concentration of NO in the samplebeing evaluated. For example, metalloporphyrins, which contain metalssuch as iron, manganese, nickel, and cobalt, are capable of binding NOand are believed to form metal nitrosyls which provide a differentoxidation or reduction potential than NO or the electrode sensor alone.The NO concentration in a sample can be determined by comparing theobserved current drawn through the electrode sensor as a workingelectrode at a fixed potential with the currents observed at the samepotential using reference samples with a known NO concentration.

In measuring NO, a two or three electrode system can be employed. Theworking electrode, comprising the coated carbon fiber, with mesh orplate, can be connected to a conductive lead wire with conductive epoxy.The lead wire connects to the voltammetric analyzer, potentiostat orcoulometric measuring instrument. The auxiliary or counterelectrodegenerally comprises a chemically inert conductive material such as anoble metal, carbon or tin indium oxide which can also be connected tothe measuring instrument with a lead wire. In a three electrode system,a reference electrode, such as a standard calomel electrode (SCE), canalso be employed and connected to the measuring instrument with a thirdconductive lead wire.

The method of detecting the presence or absence of NO in a sample,therefore, comprises connecting the NO-specific electrode sensor of thepresent invention to a potentiostat, calibrating the potentiostat andelectrode sensor for a sample known to be devoid of NO, and detectingthe presence or absence of NO in an unknown sample by comparing themeasured current to the current for the sample known to be devoid of NO.A change in the observed current indicates the presence of NO in theunknown sample. Similarly, the method of measuring the concentration ofNO in a sample comprises connecting the NO electrode sensor to apotentiostat, calibrating the potentiostat and electrode sensor forsamples of known NO concentration, and measuring NO concentration in anunknown sample by comparing the measured current to the current for thesamples of known NO concentration.

The potential applied to the electrode will depend upon the type ofpolymeric compound used to coat the substrate. The applied potential canhave a greater absolute value than the peak potential of the oxidationor reduction reaction in a cyclic voltammogram (e.g., a −0.45 V appliedpotential for a −0.40 V peak potential, or a +0.55 V applied potentialfor a +0.50 V peak potential), all relative to a reference electrodepotential.

The detection and/or measurement of NO in a sample can also beaccomplished by contacting the electrode sensor with the sample for somedetermined period of time sufficient to allow interaction of NO with theelectrochemically active polymeric coating. The electrode sensor canthen be removed from the sample. Readings from a potentiostat previouslycalibrated for known concentrations of NO, and comparing the observedcurrent with the current for the electrode sensor having been exposed tosimilar samples of known NO concentration for the same period of time.

In a variation of this embodiment, the electrode(s) can be prepared fromruthenium, or have a coating prepared from ruthenium on a core ofsupporting material. Alternatively, the ruthenium can be combined withone or more metals or non-metals as may be desired.

The body of the electrode(s) can also be wrapped with electricalshielding. The electrical shielding would not cover the portion of theelectrode used to contact the sample. The electrical shielding wouldreduce interference. Reduction of interference can be useful on numerousoccasions including using the electrode near RF medical devices, such aselectro-cauterization devices.

Superoxide Sensors

The above embodiments can be used for superoxide sensors with minormodifications. Superoxide sensors generally use differentchemoluminescent and electrically reactive chemicals than NO sensors.Reactive chemoluminescent and electrically reactive methods forsuperoxide fiber optic sensors include nitro blue tetrazolium (NO₂-TB)method, cytochrome c method, epinephrine method, pyrogallol method and6-hydroxydopamine method (Heikkla et al., Anal. Biochem. 75: 356-362,1972), and H₂O₂ measurement method, all of which are commonly used inthe art.

The principle of these superoxide dismutase (SOD) activity determinationprocesses is shown, for example, by taking the case of a process usingthe NO₂-TB method in superoxide detection system. When SOD is present inthe system, dismutation of superoxide is accelerated and the superoxideproduced becomes O₂ and H₂O₂. This superoxide also reduces cytochrome c,NO₂-TB or the like to subject the same to coloration and oxidizesepinephrine, pyrogallol, 6-hydroxydopamine or the like to subject thesame to coloration. Therefore, by utilizing this property, a decrease inabsorbance of sample with respect to reagent blank value is measured andSOD activity value can be determined.

Measuring the H₂O₂ produced by the action of SOD can also be a suitablemethod of determining superoxide levels with the sensor 12 of theguidewire 10. As a method and a reagent for quantitating H₂O₂ in the SODactivity determination process of this invention, any conventionalmethod and reagent quantitating H₂O₂ can be used. For example, allmethods for quantitating H₂O₂ by combination of peroxidase and anoxidizable color reagent can be used. Such oxidizable color reagentsinclude, for example, oxidizable color reagents consisting of acombination of 4-aminoantipyrine (4-AAP) and a phenolic compound or anN,N-disubstituted aniline series compound, combined reagents of3-methylbenzothiazolinonehydrazone (MBTH) and an aniline seriescompound, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS),triphenylmethane series leuco coloring materials, benzidine derivatives,o-tolidine derivatives, diphenylamine derivatives, triallylimidazolederivatives, o-phenylenediamine, leucomethylene blue derivatives, etc.In addition to the methods described above, a method using a combinedreagent of a tetravalent titanium compound and2-(5-bromo-2-pyridylazo)-5-(N-propyl-N-sulfopropylamino)phenol and/or asalt thereof (which can avoid using POD) can also be used forquantitating H₂O₂. For further stabilizing the oxidizable color reagentand its developed color after oxidation and coloration, the presence ofβ-cyclodextrin and/or a derivative thereof or of y-cyclodextrin can besufficient.

With respect to the concentrations of these compounds, a concentrationof β-cyclodextrin of 0.01 to 1.5 wt/vol %, that of γ-cyclodextrin of 0.1to 3 wt/vol %, that of β-cyclodextrin derivative of 0.1 to 5 wt/vol %and that of γ-cyclodextrin derivative of 0.1 to 5 wt/vol % can all beused in the solution. Mixtures of two or more of these compounds in anyratio can also be used so long as the concentrations of the compoundsare within the above-mentioned ranges.

The cyclodextrin derivative includes:

β-CD(—OH)₁₉(ONO₂)₂

β-CD(—OH)_(19.2)(OPO₃H)_(1.8)

β-CD(—OH)₁₉(OSO₃H)₂

β-CD(—OH)_(18.5)(—O—CH₂—CO₂H)_(2.5)

β-CD(—OH)_(19.3)(—O—CH₂CH₂Ch₂-SO₃H)_(1.7)

β-CD(—OH)_(18.5)(—O—CH₂Ch₂Ch₂-SO₃H)_(2.5)

β-CD(—OH)_(18.0)(—O—CH₂CH₂CH₂—SO₃H)_(3.0)

β-CD(—OH)₇(—OCH₃)₁₄

β-CD(—OCH₃)₂₁

Although all of the above listed methods for measuring superoxide levelsare well suited for use with a fiber optic detector, as described withrespect to NO fiber optic sensors above, they can also be used ascoatings on an electrode to measure electrical resistance as describedabove for NO electrode sensors.

Additional Sensors

Other sensors can be used in addition to NO and/or superoxide sensors,including those for sensing hemodynamic characteristics, hematologicalparameters related to blood and blood components, and thermal parametersof the vasculature, lesion, or body site being treated. Sensors capableof these supplemental measurements are commonly known to those havingordinary skill in the art and include fiber optic sensors.

Possible target hemodynamic characteristics or variables include bloodflow velocity and velocity profile characteristics. The detection ofstagnant or recirculating flow regions can relate to propensity of celladhesion to the endothelium, whereas the detection of slightly turbulentflow can indicate a stenosis that could be angiographically silent. Inaddition, the levels of shear force can be important for detectingdisease-prone regions or shear-induced platelet activation. There areother hemodynamic variables, such as local pressure gradient, that canalso be measured or derived from measurements by a sensor such as anoptical fiber sensor with the intent of identifying regions at high riskfor clinical complication.

Additional sensors disposed within the guidewire 10, such as opticalfiber sensors, can be capable of measuring temperature, pressure, flow,velocity, turbulence, shear stress, etc., of a treatment site. Aphysician can then use this information in making treatment decisions.For example, if the additional sensor identifies flow discontinuities orabnormal flow rates and the guidewire 10 can be operatively coupled to aballoon catheter, the physician can use this information to optimize anangioplasty. Or, if the additional sensor is disposed within theguidewire 10 that is used as a stent delivery system, the physician canuse the information to optimize the dilatation of the stent.

Method of Use

In one method of using the present invention, a medical professional(e.g. cardiologist) inserts the guidewire 10 into the patient'svasculature and advances it to a specified location in the vasculature.The sensor 12 can be selected based on the sensor's capability ofdetecting the particular physical characteristic or variable, be it NO,superoxide, presence of other molecules containing oxygen, etc. Once theguidewire 10 is in place, the data system 62 can be operated to send andreceive signals. The received signals are processed by the data system62 to provide information on a display such that the medicalprofessional can view this information and determine how to proceed.

The medical professional can choose to perform a therapeutic procedure,such as balloon angioplasty or stenting, or decide that furthertreatment is not required. The medical professional can also decide thatfurther information on that section of the vasculature is necessary andeither continue with the same guidewire-based sensor or use a differentsensor to try to obtain different physical characteristics or data.

A catheter can be operatively fitted over the guidewire 10 (althoughfitting can occur before entry of the guidewire into the patient) andthe catheter can be fed to a desired length along the guidewire. Theguidewire 10 can be completely or partially removed from the patient,leaving the catheter in place in the patient. Because the inventiveguidewire provides data of the conditions at the end of the catheter,the medical professional can choose to leave the guidewire in placewithin the patient while the catheter is also in place within thepatient.

One way to amplify biological NO response can be to administer apharamacological stimulant such as acetylcholine to increase NOproduction. With the guidewire 10 in place, the pharmacologicalstimulant could be delivered through a catheter with a lumen, through anopening in the guidewire 10, or through any device with drug deliverycapacity. The amplified NO response can be helpful to improve NOdetection and allow measurements further away from the tissue to beanalyzed. Levels of NO in stimulated, diseased tissue also can provideadditional data points for diagnostic analysis (in addition to thebaseline, unstimulated NO levels). These two sets of data points canprovide diagnostic information when compared against each other and whencompared to stimulated and unstimulated NO levels for healthy tissue.

The guidewire 10 of the present invention provides several advantagesover the relatively few current diagnostic and therapeutic devices usedin the art. The guidewire 10 can sense extremely small gradients ofrelevant chemical parameters throughout the human vascular system and inthe critical areas surrounding the treatment site to provide morecomprehensive information on the disease state. A catheter need not beused to make the guidewire functional. The guidewire can be used byitself to gather NO and/or superoxide and/or supplemental readingsbecause of the functional sensor.

Although the invention has been disclosed in terms of particularembodiments and applications, one of ordinary skill in the art, in lightof this teaching, can generate additional embodiments and modificationswithout departing from the spirit of or exceeding the scope of theclaimed invention. Accordingly, it is to be understood that the drawingsand descriptions herein are proffered by way of example to facilitatecomprehension of the invention and should not be construed to limit thescope thereof.

1. A method for performing a therapeutic procedure, comprising: providing a guidewire having an outside diameter, comprising: an elongated member including a lumen disposed along a segment of the elongated member and an opening positioned so that the lumen is in fluid communication with the vessel, a shaping ribbon having a distal and proximal end, the distal end secured to a rounded tip and the proximal end secured to a distal end of the elongated member, and a sensor positioned within the lumen so that the sensor is in fluid communication with the vessel through the opening, the sensor being capable of measuring the level of nitric oxide or superoxide in the vessel, wherein the sensor is capable of being moved independently of the distal end of the elongated member; providing a treatment catheter including a lumen having an inside diameter larger than the outside diameter to enable sliding of the treatment catheter over and along the guidewire; positioning the guidewire at a specified location within a vessel; allowing a body fluid to enter the lumen through the opening in the elongated member of the guidewire so that the body fluid is in contact with the sensor; measuring the level of nitric oxide or superoxide of the body fluid in contact with the sensor; and based on the measured level of nitric oxide or superoxide, performing the therapeutic procedure including the step of guiding a treatment catheter to the specified location by sliding the treatment catheter over and along the guidewire.
 2. The method of claim 1, wherein the vessel is a blood vessel.
 3. The method of claim 1, wherein the measuring step includes delivering, using the guidewire, a stimulant to amplify a biological nitric oxide or superoxide response to improve nitric oxide or superoxide detection by the sensor.
 4. The method of claim 3, wherein the stimulant comprises acetylcho line.
 5. The method of claim 1, wherein the designated region within the vessel is affected by thrombosis or restenosis.
 6. The method of claim 1, further comprising bending the sensor away from a central longitudinal axis of the distal end of the elongated member in order to measure the level of nitric oxide or superoxide of the body.
 7. The method of claim 1, further comprising sliding the sensor along the distal end of the elongated member in order to measure the level of nitric oxide or superoxide of the body.
 8. The method of claim 7, further comprising rotating the sensor.
 9. The method of claim 1, wherein the performing the therapeutic procedure includes the step of selecting angioplasty or stenting based on the measured levels of nitric oxide or superoxide.
 10. The method of claim 1, wherein the guidewire includes a flexible coil having a helical configuration displaced around the distal end of the elongated member.
 11. A method for performing a therapeutic procedure, comprising: providing an guidewire having an outside diameter, comprising: an elongated member including a lumen disposed along a segment of the elongated member, a sensor positioned within the lumen of the elongated member so that the sensor is in fluid communication with the vessel, the sensor being capable of measuring the level of nitric oxide or superoxide in the body fluid, wherein the sensor is capable of being moved independently of a distal end of the elongated member; and a shaping ribbon having a distal and proximal end, the distal end secured to a rounded tip and the proximal end secured to the distal end of the elongated member; providing a treatment catheter including a lumen having an inside diameter larger than the outside diameter to enable sliding of the treatment catheter over and along the guidewire; positioning the guidewire at a specified location within a vessel; allowing a body fluid to make contact with the sensor; measuring the level of nitric oxide or superoxide of the body fluid in contact with the sensor at the specified location; and based on the measured level of nitric oxide or superoxide, performing the therapeutic procedure including the step of guiding a treatment catheter to the specified location sliding the treatment catheter over and along the guidewire.
 12. The method of claim 11, wherein the vessel is a blood vessel.
 13. The method of claim 11, wherein the designated region within the vessel is affected by thrombosis or restenosis.
 14. The method of claim 11, additionally including delivering a stimulant to increase the production of nitric oxide or superoxide.
 15. The method of claim 14, wherein the stimulant comprises acetylcholine.
 16. The method of claim 11, further comprising bending the sensor away from a central longitudinal axis of the distal end of the elongated member in order to measure the level of nitric oxide or superoxide of the body.
 17. The method of claim 11, further comprising sliding the sensor along the distal end of the elongated member in order to measure the level of nitric oxide or superoxide of the body.
 18. The method of claim 17, further comprising rotating the sensor.
 19. The method of claim 11, wherein the performing the therapeutic procedure includes the step of selecting angioplasty or stenting based on the measured levels of nitric oxide or superoxide.
 20. The method of claim 11, wherein the measuring step includes delivering, using the guidewire, a stimulant to amplify a biological nitric oxide or superoxide response to improve nitric oxide or superoxide detection by the sensor.
 21. The method of claim 20, wherein the stimulant comprises acetylcho line.
 22. The method of claim 11, wherein the guidewire includes a flexible coil having a helical configuration displaced around the distal end of the elongated member.
 23. A method for performing a therapeutic procedure, comprising: providing a guidewire having an outside diameter, comprising: an elongated member including a lumen disposed along a segment of the elongated member, a tapered distal core section forming an opening, and a helical coil or polymeric jacket attached at a proximal end thereof to the distal core section and at a distal, rounded tip of the guidewire to a ribbon cable, a sensor positioned within the lumen of the elongated member so that the sensor is in fluid communication with the vessel through the opening, the sensor being capable of measuring the level of nitric oxide or superoxide in the vessel, wherein a tip of the sensor is disposable within the rounded tip when the guidewire is being advanced to the specified location within a vessel, and wherein the sensor is capable of being moved independently of the distal core section; providing a treatment catheter including a lumen having an inside diameter larger than the outside diameter to enable sliding of the treatment catheter over and along the guidewire; positioning the guidewire at a specified location within a vessel; allowing a body fluid to enter the lumen through the opening in the elongated member of the guidewire so that the body fluid is in contact with the sensor; measuring the level of nitric oxide or superoxide of the body fluid in contact with the sensor; and based on the measured level of nitric oxide or superoxide, performing the therapeutic procedure including the step of guiding a treatment catheter to the specified location by sliding the treatment catheter over and along the guidewire.
 24. A method for performing a therapeutic procedure, comprising: providing an elongated guidewire having an outside diameter, comprising: an elongated member including a lumen disposed along a segment of the elongated member, a tapered distal core section forming an opening, and a helical coil or polymeric jacket attached at a proximal end thereof to the distal core section and at a distal, rounded tip of the guidewire to a ribbon cable, a sensor positioned within the lumen, the sensor being capable of measuring the level of nitric oxide or superoxide in the body fluid, wherein the sensor is capable of being moved independently of the distal core section, and wherein a tip of the sensor is disposable within the rounded tip when the guidewire is being advanced to the specified location within a vessel; providing a treatment catheter including a lumen having an inside diameter larger than the outside diameter to enable sliding of the treatment catheter over and along the guidewire; positioning the guidewire at a specified location within a vessel; allowing a body fluid to make contact with the sensor; measuring the level of nitric oxide or superoxide of the body fluid in contact with the sensor at the specified location; and based on the measured level of nitric oxide or superoxide, performing the therapeutic procedure including the step of guiding a treatment catheter to the specified location sliding the treatment catheter over and along the guidewire. 